Vimentin: Regulating EMT and Cancer

Wed, 02/27/2013 - 12:28

Vimentin, a member of the intermediate filament (IF) family, is a protein responsible for maintaining cellular integrity and reducing damage caused by stress. The vimentin protein is ubiquitously expressed in normal mesenchymal cells, and recent research has observed a relationship in the increased level of vimentin expression and the proliferation of various epithelial, prostate, gastrointestinal, central nervous system (CNS), breast, malignant melanoma, and lung cancers (1). It is vimentin’s up-regulation in the nucleus, during epithelial-mesenchymal transition (EMT), which has been linked to a number of tumorigenic events (1, 2, 5).

IF analysis of neuron/glial cultures.

Recent studies support the notion that vimentin functions as a positive regulator of EMT and up-regulation of vimentin appears to be a prerequisite for EMT induction (6). Three novel vimentin regulators have been identified: EPHB4, WIPF2, and MTHFD2. (5). These regulators, specifically MTHFD2, have a positive correlation with vimentin expression and could potentially be used as a target for chemotherapeutic therapies that block cancer cell metastasis (5). Conversely, microRNA miR-30a negatively regulates vimentin expression by binding vimentin’s 3’-untraslated region. Overexpression of miR-30a has been shown to repress migration and invasiveness of certain breast cancer phenotypes and may prove yet another therapeutic target for cancer treatment (3). While studies into the use of vimentin as a cancer treatment continue, other recent experiments have shown that fibroblasts lacking vimentin migrate poorly, and display reduced mechanical stability, motility and directional migration towards different chemo-attractive stimuli (7). Additionally, studies into E-cadherin’s role in cervical squamous cell cancer have helped develop markers of metastasis and poor cancer prognosis. Expression of E-cadherin also shows a negative correlation with expression with vimentin. This correlation could prove to be a valuable survival indicator for patients with this type of cancer (4).